Additional integrated MMTV proviruses are found in many murine T-cell lymphomas. Athough acquisition of MMTV proviruses also occurs in MMTV-induced mammary carcinomas, a variety of features distinguish the two tumor types. (i) The additional MMTV copies in lymphomas often originate from endogenous MMTV rather than exogenous virus. (ii) Most newly acquired MMTV proviruses in lymphomas contain an LTR deletion which involves the glucocorticoid regulatory element (GRE) or enhancer and the LTR open reading frame (orf). (iii) T-cell tumors with additional MMTV proviruses lack MMTV particle production. The objective of this study is to determine the mechanism of MMTV acquisition, including deletion formation, and to assess the involvement of LTR changes in determining MMTV disease specificity. The ubiquity of the MMTV LTR alterations in lymphomas suggests that there is a common mechanism for generation and/or selection. Selection for altered promoter/enhancer activity will be tested using MMTV-driven chloramphenicol acetyl transferase (CAT) constructs. Changes in the distribution and function of orf in lymphomas and mammary cells will be assessed with antiseral against a trpE-orf fusion protein. The requirement of MMTV amplification in T-cells for intact env gene expression (and thus extracellular virus production) will be tested by nucleotide sequencing and molecular constructions involving the endogenous viruses, Mtv-8, Mtv-9, and Mtv-17. The involvement of the LTR truncations in T-cell lymphomagenesis will be evaluated by inserting the truncated LTR into mammary tumor-inducing clones which are infectious in vitro and in vivo. Primary tumors induced by T-cell tropic MMTVs will be examined for common sites of integration. This study should yield important information aobut the transmission of endogenous viruses, the tissue-specific expression of cellular genes, and the mechanism of MMTV-induced tumorigenesis.